The overarching theme of this Program will be to define basic self-renewal mechanisms of hESCs and how they become specified into different lineages. Each of the research projects is complementary but highly synergistic and built on a common biological platform. The Program places a strong emphasis on using the latest hESC culture technology and will be highly interactive with the Southeast scientific community. The 3 Projects will: - address molecular and cellular aspects of early cell fate commitment;- determine how the genome is remodeled during differentiation;- and apply state of the art technology to characterize glycosylation patterns in hESC and differentiated cells. The 3 Cores will: - function as a resource for the Program and the Southeast by maintaining and distributing hESCs, providing an intensive 2-week Training Program in hESC technology and functioning as a general technical resource;-establish new technologies designed to solve major problems that restrict progress in the hESC area;- provide administrative, logistical support for the Program and act as a conduit for interactions with the Southeast. The Program will significantly accelerate scientific advances made in the hESC area at the University of Georgia and at partnering Institutions in the Southeast. Overall, discoveries made by this team will have a major impact on our understanding of basic hESC biology and human development. All of these discoveries will be critical for the development of strategies where hESCs are to be used in cell therapies for treating degenerative disease and repair of chronic injury.